Pub Date : 2024-06-06DOI: 10.1101/2024.06.05.24308502
T. D. Eicher, R. S. Kelly, J. Braisted, J. K. Siddiqui, J. C. Celedon, C. Clish, R. E. Gerszten, S. T. Weiss, M. Mcgeachie, R. Machiraju, J. Lasky-Su, E. A. Mathe
Serum total immunoglobulin E levels (total IgE) capture the state of the immune system in relation to allergic sensitization. High levels are associated with airway obstruction and poor clinical outcomes in pediatric asthma. Inconsistent patient response to anti-IgE therapies motivates discovery of molecular mechanisms underlying serum IgE level differences in children with asthma. To uncover these mechanisms using complementary metabolomic and transcriptomic data, abundance levels of 529 named metabolites and expression levels of 22,772 genes were measured among children with asthma in the Childhood Asthma Management Program (CAMP, N=564) and the Genetic Epidemiology of Asthma in Costa Rica Study (GACRS, N=309) via the TOPMed initiative. Gene-metabolite associations dependent on IgE were identified within each cohort using multivariate linear models and were interpreted in a biochemical context using network topology, pathway and chemical enrichment, and representation within reactions. A total of 1,617 total IgE-dependent gene-metabolite associations from GACRS and 29,885 from CAMP met significance cutoffs. Of these, glycine and guanidinoacetic acid (GAA) were associated with the most genes in both cohorts, and the associations represented reactions central to glycine, serine, and threonine metabolism and arginine and proline metabolism. Pathway and chemical enrichment analysis further highlighted additional related pathways of interest. The results of this study suggest that GAA may modulate total IgE levels in two independent pediatric asthma cohorts with different characteristics, supporting the use of L-Arginine as a potential therapeutic for asthma exacerbation. Other potentially new targetable pathways are also uncovered.
{"title":"Consistent Multi-Omic Relationships Uncover Molecular Basis of Pediatric Asthma IgE Regulation","authors":"T. D. Eicher, R. S. Kelly, J. Braisted, J. K. Siddiqui, J. C. Celedon, C. Clish, R. E. Gerszten, S. T. Weiss, M. Mcgeachie, R. Machiraju, J. Lasky-Su, E. A. Mathe","doi":"10.1101/2024.06.05.24308502","DOIUrl":"https://doi.org/10.1101/2024.06.05.24308502","url":null,"abstract":"Serum total immunoglobulin E levels (total IgE) capture the state of the immune system in relation to allergic sensitization. High levels are associated with airway obstruction and poor clinical outcomes in pediatric asthma. Inconsistent patient response to anti-IgE therapies motivates discovery of molecular mechanisms underlying serum IgE level differences in children with asthma. To uncover these mechanisms using complementary metabolomic and transcriptomic data, abundance levels of 529 named metabolites and expression levels of 22,772 genes were measured among children with asthma in the Childhood Asthma Management Program (CAMP, N=564) and the Genetic Epidemiology of Asthma in Costa Rica Study (GACRS, N=309) via the TOPMed initiative. Gene-metabolite associations dependent on IgE were identified within each cohort using multivariate linear models and were interpreted in a biochemical context using network topology, pathway and chemical enrichment, and representation within reactions. A total of 1,617 total IgE-dependent gene-metabolite associations from GACRS and 29,885 from CAMP met significance cutoffs. Of these, glycine and guanidinoacetic acid (GAA) were associated with the most genes in both cohorts, and the associations represented reactions central to glycine, serine, and threonine metabolism and arginine and proline metabolism. Pathway and chemical enrichment analysis further highlighted additional related pathways of interest. The results of this study suggest that GAA may modulate total IgE levels in two independent pediatric asthma cohorts with different characteristics, supporting the use of L-Arginine as a potential therapeutic for asthma exacerbation. Other potentially new targetable pathways are also uncovered.","PeriodicalId":506788,"journal":{"name":"medRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141265147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-06DOI: 10.1101/2024.06.05.24308510
Jenna Demedis, MA JuliaReedy, MS KristenMiller, PhD Junxiao Hu, J. Klosky, B. Holliman, P. N. P. M. Mph, E. J. C. M. Mph, Christina R. Studts
Background: Approximately 20-50% of adolescent and young adult-aged childhood cancer survivors (AYA-CCS) experience sexual dysfunction (SD), although this healthcare need is widely underrecognized. Previous research from both AYA-CCS patients and their providers report that SD needs are unaddressed despite patient desires for SD discussions to be incorporated as part of their care. Patients and providers agree that standardized use of a patient-reported outcome measure may facilitate SD discussions; an SD screening approach was developed with patient and provider input. This study will measure the effectiveness of a standardized SD screening intervention and assess implementation outcomes and multilevel barriers and facilitators to guide future research. Methods: This multi-site, mixed methods, type 1 effectiveness-implementation hybrid trial will be evaluated using a pre-post design (NCT05524610). The trial will enroll 86 AYA-CCS (ages 15-39) from two cancer centers in the United States. The SD intervention consists of core fundamental functions with a "menu" of intervention options to allow for flexibility in delivery and tailoring in variable contexts. Effectiveness of the intervention on facilitating SD communication will be measured through patient surveys and clinical data; multivariable logistic regression will be used for the binary outcome of self-reported SD screening, controlling for patient-level predictors. Implementation outcomes will be assessed using mixed methods (electronic health record abstraction, patient and provider surveys, and provider interviews. Quantitative and qualitative findings will be merged using a joint display to understand factors affecting intervention success. Implications: Identification and treatment of SD in AYA-CCS is an important and challenging quality of life concern. The type 1 hybrid design will facilitate rapid translation from research to practice by testing the effects of the intervention while simultaneously identifying multilevel barriers and facilitators to real-world implementation. This approach will inform future testing and dissemination of the SD screening intervention.
{"title":"Testing effectiveness and implementation of a standardized approach to sexual dysfunction screening among adolescent and young adult-aged survivors of childhood cancer: A type I hybrid, mixed methods trial protocol","authors":"Jenna Demedis, MA JuliaReedy, MS KristenMiller, PhD Junxiao Hu, J. Klosky, B. Holliman, P. N. P. M. Mph, E. J. C. M. Mph, Christina R. Studts","doi":"10.1101/2024.06.05.24308510","DOIUrl":"https://doi.org/10.1101/2024.06.05.24308510","url":null,"abstract":"Background: Approximately 20-50% of adolescent and young adult-aged childhood cancer survivors (AYA-CCS) experience sexual dysfunction (SD), although this healthcare need is widely underrecognized. Previous research from both AYA-CCS patients and their providers report that SD needs are unaddressed despite patient desires for SD discussions to be incorporated as part of their care. Patients and providers agree that standardized use of a patient-reported outcome measure may facilitate SD discussions; an SD screening approach was developed with patient and provider input. This study will measure the effectiveness of a standardized SD screening intervention and assess implementation outcomes and multilevel barriers and facilitators to guide future research. Methods: This multi-site, mixed methods, type 1 effectiveness-implementation hybrid trial will be evaluated using a pre-post design (NCT05524610). The trial will enroll 86 AYA-CCS (ages 15-39) from two cancer centers in the United States. The SD intervention consists of core fundamental functions with a \"menu\" of intervention options to allow for flexibility in delivery and tailoring in variable contexts. Effectiveness of the intervention on facilitating SD communication will be measured through patient surveys and clinical data; multivariable logistic regression will be used for the binary outcome of self-reported SD screening, controlling for patient-level predictors. Implementation outcomes will be assessed using mixed methods (electronic health record abstraction, patient and provider surveys, and provider interviews. Quantitative and qualitative findings will be merged using a joint display to understand factors affecting intervention success. Implications: Identification and treatment of SD in AYA-CCS is an important and challenging quality of life concern. The type 1 hybrid design will facilitate rapid translation from research to practice by testing the effects of the intervention while simultaneously identifying multilevel barriers and facilitators to real-world implementation. This approach will inform future testing and dissemination of the SD screening intervention.","PeriodicalId":506788,"journal":{"name":"medRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141265191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-06DOI: 10.1101/2024.06.05.24308497
A. Fola, T. Kobayashi, T. Shields, H. Hamapumbu, M. Musonda, B. Katowa, J. Matoba, J. Stevenson, Douglas E. Norris, P. Thuma, Amy Wesolowski, William J Moss, Jonathan J. Juliano, J. A. Bailey, Claverick Street, RM314A
The emergence of antimalarial drug resistance is an impediment to malaria control and elimination in Africa. Analysis of temporal trends in molecular markers of resistance is critical to inform policy makers and guide malaria treatment guidelines. In a low and seasonal transmission region of southern Zambia, we successfully genotyped 85.5% (389/455) of Plasmodium falciparum samples collected between 2013-2018 from 8 spatially clustered health centres using molecular inversion probes (MIPs) targeting key drug resistance genes. Aside from one sample carrying K13 R622I, none of the isolates carried other World Health Organization-validated or candidate artemisinin partial resistance (ART-R) mutations in K13. However, 13% (CI, 9.6-17.2) of isolates had the AP2MU S160N mutation, which has been associated with delayed clearance following artemisinin combination therapy in Africa. This mutation increased in prevalence between 2015-2018 and bears a genomic signature of selection. During this time period, there was an increase in the MDR1 NFD haplotype that is associated with reduced susceptibility to lumefantrine. Sulfadoxine-pyrimethamine polymorphisms were near fixation. While validated ART-R mutations are rare, a mutation associated with slow parasite clearance in Africa appears to be under selection in southern Zambia.
{"title":"Temporal genomic analysis of Plasmodium falciparum reveals increased prevalence of mutations associated with delayed clearance following treatment with artemisinin-lumefantrine in Choma District, Southern Province, Zambia","authors":"A. Fola, T. Kobayashi, T. Shields, H. Hamapumbu, M. Musonda, B. Katowa, J. Matoba, J. Stevenson, Douglas E. Norris, P. Thuma, Amy Wesolowski, William J Moss, Jonathan J. Juliano, J. A. Bailey, Claverick Street, RM314A","doi":"10.1101/2024.06.05.24308497","DOIUrl":"https://doi.org/10.1101/2024.06.05.24308497","url":null,"abstract":"The emergence of antimalarial drug resistance is an impediment to malaria control and elimination in Africa. Analysis of temporal trends in molecular markers of resistance is critical to inform policy makers and guide malaria treatment guidelines. In a low and seasonal transmission region of southern Zambia, we successfully genotyped 85.5% (389/455) of Plasmodium falciparum samples collected between 2013-2018 from 8 spatially clustered health centres using molecular inversion probes (MIPs) targeting key drug resistance genes. Aside from one sample carrying K13 R622I, none of the isolates carried other World Health Organization-validated or candidate artemisinin partial resistance (ART-R) mutations in K13. However, 13% (CI, 9.6-17.2) of isolates had the AP2MU S160N mutation, which has been associated with delayed clearance following artemisinin combination therapy in Africa. This mutation increased in prevalence between 2015-2018 and bears a genomic signature of selection. During this time period, there was an increase in the MDR1 NFD haplotype that is associated with reduced susceptibility to lumefantrine. Sulfadoxine-pyrimethamine polymorphisms were near fixation. While validated ART-R mutations are rare, a mutation associated with slow parasite clearance in Africa appears to be under selection in southern Zambia.","PeriodicalId":506788,"journal":{"name":"medRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141265235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-06DOI: 10.1101/2024.06.05.24308504
S. Sekimitsu, BS Omar Alaa Halawa, Michael V. Boland, PhD Nazlee Zebardast
Introduction: The gender pay gap is wide in medicine but the extent of this disparity across specialties and over time have not been elucidated. Here we evaluate differences in Medicare reimbursement between men and women physicians over time and by specialty, controlling for physician and practice characteristics. Methods: The Centers for Medicare & Medicaid Services Payment Data was used to determine total reimbursements and number of services submitted by physicians practicing in the US between 2013 and 2019. Data from the American Community Survey (ACS) were used to determine average income, unemployment rates, poverty rates, income, and educational attainment levels by zip code for each physician's practice location. Results: Among the 3,831,504 physicians included in this analysis from 2013-2019, 2,712,545 (70.8%) were men and 1,118,859 (29.2%) were women. Overall, men received more in Medicare reimbursements ($58,815 +/- $104,772 vs. $32,205 +/- $60,556, p<0.001) and billed more services (864 +/- 1,780 vs. 505 +/- 1,007, p<0.001) compared to women. The median Medicare reimbursement for men decreased from 2013 to 2019 from $59,710 to $57,874, while the median Medicare reimbursement for women increased from $30,575 to $33,456. Men were reimbursed more than women across all specialties with the greatest disparity in procedure-heavy specialties. The specialties with the highest difference in median Medicare reimbursement between men and women were ophthalmology ($99,452), dermatology ($84,844), cardiology ($64,112), nephrology ($62,352), and pulmonary medicine ($47,399). In linear regression models controlling for calendar year, years of experience, total number of services, and ACS zip-code-level variables, men received a higher amount of Medicare reimbursement in all specialties, as compared to women (p<0.01 for all). The percentage of top earning men (range: 65.0%-99.5%) surpassed the proportion of men in each specialty (range: 46.1%-94.6%), except public health and preventive medicine. Conclusions and Relevance: Women physicians continue to receive lower total Medicare reimbursements than men physicians, particularly in procedure-heavy specialties. Lower clinical volume and fewer procedural services among women physicians partially contribute to the disparities in reimbursement.
{"title":"Gender based disparities in Medicare physician reimbursement persist across years and specialty","authors":"S. Sekimitsu, BS Omar Alaa Halawa, Michael V. Boland, PhD Nazlee Zebardast","doi":"10.1101/2024.06.05.24308504","DOIUrl":"https://doi.org/10.1101/2024.06.05.24308504","url":null,"abstract":"Introduction: The gender pay gap is wide in medicine but the extent of this disparity across specialties and over time have not been elucidated. Here we evaluate differences in Medicare reimbursement between men and women physicians over time and by specialty, controlling for physician and practice characteristics. Methods: The Centers for Medicare & Medicaid Services Payment Data was used to determine total reimbursements and number of services submitted by physicians practicing in the US between 2013 and 2019. Data from the American Community Survey (ACS) were used to determine average income, unemployment rates, poverty rates, income, and educational attainment levels by zip code for each physician's practice location. Results: Among the 3,831,504 physicians included in this analysis from 2013-2019, 2,712,545 (70.8%) were men and 1,118,859 (29.2%) were women. Overall, men received more in Medicare reimbursements ($58,815 +/- $104,772 vs. $32,205 +/- $60,556, p<0.001) and billed more services (864 +/- 1,780 vs. 505 +/- 1,007, p<0.001) compared to women. The median Medicare reimbursement for men decreased from 2013 to 2019 from $59,710 to $57,874, while the median Medicare reimbursement for women increased from $30,575 to $33,456. Men were reimbursed more than women across all specialties with the greatest disparity in procedure-heavy specialties. The specialties with the highest difference in median Medicare reimbursement between men and women were ophthalmology ($99,452), dermatology ($84,844), cardiology ($64,112), nephrology ($62,352), and pulmonary medicine ($47,399). In linear regression models controlling for calendar year, years of experience, total number of services, and ACS zip-code-level variables, men received a higher amount of Medicare reimbursement in all specialties, as compared to women (p<0.01 for all). The percentage of top earning men (range: 65.0%-99.5%) surpassed the proportion of men in each specialty (range: 46.1%-94.6%), except public health and preventive medicine. Conclusions and Relevance: Women physicians continue to receive lower total Medicare reimbursements than men physicians, particularly in procedure-heavy specialties. Lower clinical volume and fewer procedural services among women physicians partially contribute to the disparities in reimbursement.","PeriodicalId":506788,"journal":{"name":"medRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141265136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-06DOI: 10.1101/2024.06.05.24308512
M. Webster, S. Manoukian, J. H. McKendrick, O. Biosca
Aims To explore the prevalence of a mental health gender gap within a young adult sample during the COVID-19 pandemic, and to identify the impact of loneliness and domestic time use on young peoples, and particularly young womens mental health. Method Using data from the UK Longitudinal Household Survey (UKHLS), this research examines mental health prior to the pandemic (2019) and during the pandemic (April 2020 until September 2021). A random-effects regression analysis was conducted to examine the effects of loneliness, and domestic factors across age and gender to ascertain their contribution to the mental health gender gap in a young adult population. Results Average mental health decline was consistently higher for women compared to men, and young people (ages 16-24) saw a reduction in mental health twice as much as those in the oldest age category (over 65). Loneliness accounted for a share of the mental health gender gap, and a more decrease in mental health was recorded for young women experiencing loneliness, compared to older age groups. Domestic and familial factors did not have a significant impact on young people's mental health. Conclusions Although across all ages and genders, mental health had returned to near pre-pandemic levels by September 2021, young people and especially women continue to have worse mental health compared to other age groups, which is consistent with pre-COVID age and gender inequalities. Loneliness is a key driver in gendered mental health inequalities during the pandemic in a young adult population.
{"title":"Exploring the Gender Gap in Young Adult Mental Health during COVID-19: Evidence from the UK","authors":"M. Webster, S. Manoukian, J. H. McKendrick, O. Biosca","doi":"10.1101/2024.06.05.24308512","DOIUrl":"https://doi.org/10.1101/2024.06.05.24308512","url":null,"abstract":"Aims To explore the prevalence of a mental health gender gap within a young adult sample during the COVID-19 pandemic, and to identify the impact of loneliness and domestic time use on young peoples, and particularly young womens mental health. Method Using data from the UK Longitudinal Household Survey (UKHLS), this research examines mental health prior to the pandemic (2019) and during the pandemic (April 2020 until September 2021). A random-effects regression analysis was conducted to examine the effects of loneliness, and domestic factors across age and gender to ascertain their contribution to the mental health gender gap in a young adult population. Results Average mental health decline was consistently higher for women compared to men, and young people (ages 16-24) saw a reduction in mental health twice as much as those in the oldest age category (over 65). Loneliness accounted for a share of the mental health gender gap, and a more decrease in mental health was recorded for young women experiencing loneliness, compared to older age groups. Domestic and familial factors did not have a significant impact on young people's mental health. Conclusions Although across all ages and genders, mental health had returned to near pre-pandemic levels by September 2021, young people and especially women continue to have worse mental health compared to other age groups, which is consistent with pre-COVID age and gender inequalities. Loneliness is a key driver in gendered mental health inequalities during the pandemic in a young adult population.","PeriodicalId":506788,"journal":{"name":"medRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141265140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-06DOI: 10.1101/2024.06.05.24308479
S. Miyamoto, K. Numakura, R. Kinoshita, T. Arashiro, H. Takahashi, H. Hibino, M. Hayakawa, T. Kanno, A. Sataka, A. Ainai, S. Arai, M. Suzuki, D. Yoneoka, T. Wakita, T. Suzuki
Background In 2024, there was quite high seroprevalence of anti-spike (S) protein antibodies against SARS-CoV-2 in Japanese adults, owing to the high vaccination coverage by spike-based vaccines. Nevertheless, the COVID-19 epidemic continues, albeit with low rates of severe illness, and hybrid immunity holders are becoming more common in these populations. It is necessary to determine the immunological protection correlates against SARS-CoV-2 re-infection in individuals with hybrid immunity because the currently available immune correlates were established by analyzing individuals possessing vaccine-induced immunity only. Methods We conducted an ad hoc prospective cohort study to measure serum anti-SARS-CoV-2 antibody levels in 4,496 Japanese adults as part of the national COVID-19 seroepidemiological survey. This ad hoc study evaluated the correlation between anti-S and anti-nucleocapsid (N) antibody levels at the first visit and their effectiveness in infection prevention until the second visit, including undiagnosed re-infections during the Omicron BA.5 epidemic period from December 2022 to March 2023. Findings We assessed the combined effect of anti-N and anti-S antibody levels and found that the reduced infection risk associated with anti-S antibody levels was limited. Contrastingly, higher levels of anti-N antibodies were strongly linked to a reduced infection risk in the entire cohort and in individuals with hybrid immunity. Interpretation We demonstrate a high correlation between reduced re-infection risk in hybrid immunity holders and high serum anti-N antibody levels, highlighting its potential as an immunological surrogate of protection against SARS-CoV-2 re-infection. The findings indicate that individuals with hybrid immunity are protected by a distinct form of immunity, beyond the presence of serum anti-S antibodies, which correlates with serum anti-N antibody levels. Funding The national COVID-19 seroepidemiological survey as a public health investigation was funded by the Ministry of Health, Labour and Welfare of Japan (MHLW). The ad hoc study based on the survey data as a research activity was funded by the Japan Agency for Medical Research and Development (AMED).
背景 2024 年，由于尖头疫苗的高接种率，日本成年人抗 SARS-CoV-2 的抗尖头（S）蛋白抗体的血清流行率相当高。尽管如此，COVID-19 疫情仍在继续，尽管重症发病率较低，而且混合免疫持有者在这些人群中越来越常见。有必要确定混合免疫个体对 SARS-CoV-2 再感染的免疫保护相关性，因为目前可用的免疫相关性是通过分析仅具有疫苗诱导免疫的个体建立的。方法 我们进行了一项特别的前瞻性队列研究，测量了 4496 名日本成年人的血清抗 SARS-CoV-2 抗体水平，这是全国 COVID-19 血清流行病学调查的一部分。这项特别研究评估了首次就诊时抗 S 抗体和抗核头壳 (N) 抗体水平与第二次就诊前预防感染效果之间的相关性，包括 2022 年 12 月至 2023 年 3 月 Omicron BA.5 流行期间未确诊的再感染病例。研究结果 我们评估了抗 N 抗体和抗 S 抗体水平的综合效果，发现抗 S 抗体水平降低的感染风险有限。相反，抗 N 抗体水平越高，整个人群和混合免疫个体的感染风险就越低。解释 我们证明了混合免疫力持有者再感染风险的降低与高血清抗 N 抗体水平之间的高度相关性，突出了其作为防止 SARS-CoV-2 再感染的免疫学替代物的潜力。研究结果表明，除了血清中的抗S抗体外，具有混合免疫力的个体还受到一种独特形式的免疫力的保护，这种免疫力与血清中的抗N抗体水平相关。资助 作为一项公共卫生调查，全国 COVID-19 血清流行病学调查由日本厚生劳动省（MHLW）资助。基于调查数据的特别研究作为一项研究活动，得到了日本医学研究开发机构（AMED）的资助。
{"title":"Serum anti-nucleocapsid antibody level induced after primary infection is an immunological surrogate of protection against SARS-CoV-2 re-infection in hybrid immunity holders","authors":"S. Miyamoto, K. Numakura, R. Kinoshita, T. Arashiro, H. Takahashi, H. Hibino, M. Hayakawa, T. Kanno, A. Sataka, A. Ainai, S. Arai, M. Suzuki, D. Yoneoka, T. Wakita, T. Suzuki","doi":"10.1101/2024.06.05.24308479","DOIUrl":"https://doi.org/10.1101/2024.06.05.24308479","url":null,"abstract":"Background In 2024, there was quite high seroprevalence of anti-spike (S) protein antibodies against SARS-CoV-2 in Japanese adults, owing to the high vaccination coverage by spike-based vaccines. Nevertheless, the COVID-19 epidemic continues, albeit with low rates of severe illness, and hybrid immunity holders are becoming more common in these populations. It is necessary to determine the immunological protection correlates against SARS-CoV-2 re-infection in individuals with hybrid immunity because the currently available immune correlates were established by analyzing individuals possessing vaccine-induced immunity only. Methods We conducted an ad hoc prospective cohort study to measure serum anti-SARS-CoV-2 antibody levels in 4,496 Japanese adults as part of the national COVID-19 seroepidemiological survey. This ad hoc study evaluated the correlation between anti-S and anti-nucleocapsid (N) antibody levels at the first visit and their effectiveness in infection prevention until the second visit, including undiagnosed re-infections during the Omicron BA.5 epidemic period from December 2022 to March 2023. Findings We assessed the combined effect of anti-N and anti-S antibody levels and found that the reduced infection risk associated with anti-S antibody levels was limited. Contrastingly, higher levels of anti-N antibodies were strongly linked to a reduced infection risk in the entire cohort and in individuals with hybrid immunity. Interpretation We demonstrate a high correlation between reduced re-infection risk in hybrid immunity holders and high serum anti-N antibody levels, highlighting its potential as an immunological surrogate of protection against SARS-CoV-2 re-infection. The findings indicate that individuals with hybrid immunity are protected by a distinct form of immunity, beyond the presence of serum anti-S antibodies, which correlates with serum anti-N antibody levels. Funding The national COVID-19 seroepidemiological survey as a public health investigation was funded by the Ministry of Health, Labour and Welfare of Japan (MHLW). The ad hoc study based on the survey data as a research activity was funded by the Japan Agency for Medical Research and Development (AMED).","PeriodicalId":506788,"journal":{"name":"medRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141265196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-06DOI: 10.1101/2024.06.05.24308520
H. Kussaibi, E. Alibrahim, E. Alamer, G. Alhaji, S. Alshehab, Z. Shabib, N. Alsafwani, R. G. Meneses
Background: Ovarian cancer is the leading cause of gynecological cancer deaths due to late diagnosis and high recurrence rates. While histopathological analysis is the gold standard for diagnosis, artificial intelligence (AI) models have shown promise in accurately classifying ovarian cancer subtypes from histopathology images. Herein, we developed an AI pipeline for automated identification of epithelial ovarian cancer (EOC) subtypes based on histopathology images and evaluated its performance compared to the pathologists' diagnosis. Methods: A dataset of over 2 million image tiles from 82 whole slide images (WSIs) of the major EOC subtypes (clear cell, endometrioid, mucinous, serous) was curated from public and institutional sources. A convolutional neural network (ResNet50) was used to extract features which were then input to classifiers (CNN, and LightGBM) to predict the cancer subtype. Results: Both AI classifiers achieved patch-level accuracy (97-98%) on the test set. Furthermore, adding a class-weighted cross-entropy loss function to the pipeline showed better discriminative performance between the subtypes. Conclusion: AI models trained on histopathology image data can accurately classify EOC subtypes, potentially assisting pathologists and reducing subjectivity in ovarian cancer diagnosis.
{"title":"Al-Powered classification of Ovarian cancers Based on Histopathological lmages","authors":"H. Kussaibi, E. Alibrahim, E. Alamer, G. Alhaji, S. Alshehab, Z. Shabib, N. Alsafwani, R. G. Meneses","doi":"10.1101/2024.06.05.24308520","DOIUrl":"https://doi.org/10.1101/2024.06.05.24308520","url":null,"abstract":"Background: Ovarian cancer is the leading cause of gynecological cancer deaths due to late diagnosis and high recurrence rates. While histopathological analysis is the gold standard for diagnosis, artificial intelligence (AI) models have shown promise in accurately classifying ovarian cancer subtypes from histopathology images. Herein, we developed an AI pipeline for automated identification of epithelial ovarian cancer (EOC) subtypes based on histopathology images and evaluated its performance compared to the pathologists' diagnosis. Methods: A dataset of over 2 million image tiles from 82 whole slide images (WSIs) of the major EOC subtypes (clear cell, endometrioid, mucinous, serous) was curated from public and institutional sources. A convolutional neural network (ResNet50) was used to extract features which were then input to classifiers (CNN, and LightGBM) to predict the cancer subtype. Results: Both AI classifiers achieved patch-level accuracy (97-98%) on the test set. Furthermore, adding a class-weighted cross-entropy loss function to the pipeline showed better discriminative performance between the subtypes. Conclusion: AI models trained on histopathology image data can accurately classify EOC subtypes, potentially assisting pathologists and reducing subjectivity in ovarian cancer diagnosis.","PeriodicalId":506788,"journal":{"name":"medRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141265271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-06DOI: 10.1101/2024.06.05.24308532
Rahul Naresh Wasnik, Matthew Cope, Aaron Cowan, Smita Pakhale, Dr. Smith Pakhale, MSc Epi Biostat Frcpc
Introduction Chronic respiratory diseases such as asthma, COPD, and other pulmonary conditions impose a substantial global health burden, affecting millions of individuals worldwide. These conditions are characterized by persistent respiratory symptoms and reduced airflow, significantly impacting quality of life, and increasing healthcare needs. Treatment typically involves the use of inhaler devices to administer medications directly to the lungs, which decreases symptoms and improves outcomes. However, the efficacy of inhaler devices is influenced by various factors, including the type of device, patient adherence, and the correct device usage by patients. In addition to clinical considerations, the environmental impact of inhaler devices, including their carbon footprint, as well as the cost implications for both healthcare systems and patients, are critical factors that require comprehensive evaluation. It is essential to develop sustainable and economically viable treatment strategies that address these considerations. Methods and Analysis We will conduct a systematic review aimed at providing a comprehensive understanding of the implications of inhaler use in treating asthma, COPD, and other chronic conditions requiring pulmonary drug delivery. Our focus will be on assessing efficiency, environmental sustainability, and cost-effectiveness. Studies lacking economic models or evaluations, without in-vivo deposition in the lungs, lacking assessment of the environmental impact of inhalers, not published in English, or falling into categories such as systematic reviews, letters, editorials, animal studies, or case studies will be excluded from this review. The primary outcome of interest in this systematic review is the efficacy of medication deposition in the lungs of individuals with respiratory diseases when using different types of inhalers. The secondary outcome is to determine their economic costs and the tertiary outcome is to evaluate the overall environmental footprints of inhalers. We will search for original research articles published until May 30, 2023, using databases such as MEDLINE (OVID), EMBASE (OVID), CENTRAL (OVID), the Canadian Drug and Health Technology Agency, and the US Food & Drug Administration. Our search method follows the PRISMA guidelines 2020. To determine study eligibility, a two-phase screening process will be conducted by three independent reviewers, with predefined outcomes extracted from eligible studies. The study will summarize findings through a narrative synthesis, using statistical analyses and sensitivity tests. In addition, funnel plots and Eggers test will be used for lung deposition analysis, while descriptive statistics will further compare costs and summarize environmental effects. We have ensured that a thorough risk of bias evaluation is part of this research approach, and it is carried out by three independent reviewers using a wide variety of tools according to the type of study. Ethics and Diss
{"title":"Assessing drug deposition efficacies, environmental impact and affordability for inhalers among chronic respiratory diseases: A systematic review","authors":"Rahul Naresh Wasnik, Matthew Cope, Aaron Cowan, Smita Pakhale, Dr. Smith Pakhale, MSc Epi Biostat Frcpc","doi":"10.1101/2024.06.05.24308532","DOIUrl":"https://doi.org/10.1101/2024.06.05.24308532","url":null,"abstract":"Introduction Chronic respiratory diseases such as asthma, COPD, and other pulmonary conditions impose a substantial global health burden, affecting millions of individuals worldwide. These conditions are characterized by persistent respiratory symptoms and reduced airflow, significantly impacting quality of life, and increasing healthcare needs. Treatment typically involves the use of inhaler devices to administer medications directly to the lungs, which decreases symptoms and improves outcomes. However, the efficacy of inhaler devices is influenced by various factors, including the type of device, patient adherence, and the correct device usage by patients. In addition to clinical considerations, the environmental impact of inhaler devices, including their carbon footprint, as well as the cost implications for both healthcare systems and patients, are critical factors that require comprehensive evaluation. It is essential to develop sustainable and economically viable treatment strategies that address these considerations. Methods and Analysis We will conduct a systematic review aimed at providing a comprehensive understanding of the implications of inhaler use in treating asthma, COPD, and other chronic conditions requiring pulmonary drug delivery. Our focus will be on assessing efficiency, environmental sustainability, and cost-effectiveness. Studies lacking economic models or evaluations, without in-vivo deposition in the lungs, lacking assessment of the environmental impact of inhalers, not published in English, or falling into categories such as systematic reviews, letters, editorials, animal studies, or case studies will be excluded from this review. The primary outcome of interest in this systematic review is the efficacy of medication deposition in the lungs of individuals with respiratory diseases when using different types of inhalers. The secondary outcome is to determine their economic costs and the tertiary outcome is to evaluate the overall environmental footprints of inhalers. We will search for original research articles published until May 30, 2023, using databases such as MEDLINE (OVID), EMBASE (OVID), CENTRAL (OVID), the Canadian Drug and Health Technology Agency, and the US Food & Drug Administration. Our search method follows the PRISMA guidelines 2020. To determine study eligibility, a two-phase screening process will be conducted by three independent reviewers, with predefined outcomes extracted from eligible studies. The study will summarize findings through a narrative synthesis, using statistical analyses and sensitivity tests. In addition, funnel plots and Eggers test will be used for lung deposition analysis, while descriptive statistics will further compare costs and summarize environmental effects. We have ensured that a thorough risk of bias evaluation is part of this research approach, and it is carried out by three independent reviewers using a wide variety of tools according to the type of study. Ethics and Diss","PeriodicalId":506788,"journal":{"name":"medRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141265148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-06DOI: 10.1101/2024.06.05.24308501
PhD Ryan Richard Ru
Background: School-based caries prevention using silver diamine fluoride (SDF) has been shown to effectively prevent and control dental caries. To better inform program design and implementation, this paper estimated transition probabilities for dental caries in a school SDF program. Methods: The CariedAway project was a pragmatic, cluster-randomized trial of school-based caries prevention interventions conducted in predominately low-income minority children. For children in CariedAway receiving SDF, transition probabilities were computed between sound, carious, and arrested states for 6-year molars using multistate Markov models. Subject-level transition probabilities over one- and two-year periods were then calculated by aggregating states of all 6-year molars and first and second bicuspids. Results: A total of 7418 children were enrolled in CariedAway, of which 1352 met inclusion criteria for this study. Of eligible participants, the baseline prevalence of untreated decay was 29% and the prevalence of dental sealants was 8%. The probability of transitioning between sound and carious states in 6-year molars ranged from 0.0022 to 0.0074. At the subject-level, the sound to carious transition probabilities were 0.07 and 0.12 after one and two years, respectively. Once in a fully arrested state, the probability of remaining arrested was 0.72 and 0.60 after one and two years. Conclusions: The overall probabilities of teeth remaining in diseased-free or arrested states was high after receiving silver diamine fluoride, although multiple applications might be needed for consistent caries arrest.
{"title":"Transition probabilities for dental caries in a school-based prevention program: A randomized clinical trial","authors":"PhD Ryan Richard Ru","doi":"10.1101/2024.06.05.24308501","DOIUrl":"https://doi.org/10.1101/2024.06.05.24308501","url":null,"abstract":"Background: School-based caries prevention using silver diamine fluoride (SDF) has been shown to effectively prevent and control dental caries. To better inform program design and implementation, this paper estimated transition probabilities for dental caries in a school SDF program. Methods: The CariedAway project was a pragmatic, cluster-randomized trial of school-based caries prevention interventions conducted in predominately low-income minority children. For children in CariedAway receiving SDF, transition probabilities were computed between sound, carious, and arrested states for 6-year molars using multistate Markov models. Subject-level transition probabilities over one- and two-year periods were then calculated by aggregating states of all 6-year molars and first and second bicuspids. Results: A total of 7418 children were enrolled in CariedAway, of which 1352 met inclusion criteria for this study. Of eligible participants, the baseline prevalence of untreated decay was 29% and the prevalence of dental sealants was 8%. The probability of transitioning between sound and carious states in 6-year molars ranged from 0.0022 to 0.0074. At the subject-level, the sound to carious transition probabilities were 0.07 and 0.12 after one and two years, respectively. Once in a fully arrested state, the probability of remaining arrested was 0.72 and 0.60 after one and two years. Conclusions: The overall probabilities of teeth remaining in diseased-free or arrested states was high after receiving silver diamine fluoride, although multiple applications might be needed for consistent caries arrest.","PeriodicalId":506788,"journal":{"name":"medRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141265209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-06DOI: 10.1101/2024.06.05.24308531
R. Cherodian, M. Franklin, S. Baxter, J. Chilcott, D. Gillespie
Background Patients seen by National Health Service (NHS) hospitals in England should now be asked if they smoke on admission. People who smoke should be treated for tobacco dependence in hospital, then offered support to quit outside of hospital. One way to support post-hospital quitting is through referring patients to community stop smoking services (CSSS). In 2024, the government announced a doubling of CSSS funding for five-years to improve reach and outcomes. Our study aimed to describe the quit rates of people referred from hospital to CSSS, alongside investigating individual characteristics associated with quitting success to inform the potential for more cost-effective, targeted support in the future. Methods The study was part of a service evaluation using real-world data collected via a CSSS electronic record system in England, which received referrals from hospital-based tobacco teams. We compared CSSS activity and quitting outcomes to local and national reporting data. Generalised Linear Models were used to investigate quitting outcomes 4-weeks after baseline in relation to demographic, socio-economic, nicotine dependence, intervention, and health factors hypothesised to be associated with quitting outcomes. Results Hospital-referred patients comprised 26% of CSSS referrals, tended to be older, with lower socio-economic status and more long-term health conditions. Overall quitting success by people who made a CSSS supported quit attempt was 61% at 4-weeks, slightly lower than local averages, but similar to national averages. Our analysis sample contained records of 1,326 quit attempts that were supported by CSSS. Of the variables investigated, we found that receiving free NHS prescriptions was consistently associated with lower quitting success (Odds Ratio [OR] 0.55, 95% Confidence Interval [CI] 0.33-0.92), potentially because this is a proxy for lower socio-economic and health status. After accounting for other factors, having cancer relative to no health conditions was associated with higher quitting success (OR 2.26, 95%CI 1.18-4.33). Conclusion Ensuring patients continue seeking support to quit smoking after their interaction with hospital-based services can lead to quit rates comparable to other CSSS attendees who make a quit attempt. Our analyses highlight the importance of hospital and CSSS investment in improving the transfer of care between services.
{"title":"Smoking Cessation after Transitioning from Hospital to Community Stop Smoking Services: Insights from Real-world Data Analysis","authors":"R. Cherodian, M. Franklin, S. Baxter, J. Chilcott, D. Gillespie","doi":"10.1101/2024.06.05.24308531","DOIUrl":"https://doi.org/10.1101/2024.06.05.24308531","url":null,"abstract":"Background Patients seen by National Health Service (NHS) hospitals in England should now be asked if they smoke on admission. People who smoke should be treated for tobacco dependence in hospital, then offered support to quit outside of hospital. One way to support post-hospital quitting is through referring patients to community stop smoking services (CSSS). In 2024, the government announced a doubling of CSSS funding for five-years to improve reach and outcomes. Our study aimed to describe the quit rates of people referred from hospital to CSSS, alongside investigating individual characteristics associated with quitting success to inform the potential for more cost-effective, targeted support in the future. Methods The study was part of a service evaluation using real-world data collected via a CSSS electronic record system in England, which received referrals from hospital-based tobacco teams. We compared CSSS activity and quitting outcomes to local and national reporting data. Generalised Linear Models were used to investigate quitting outcomes 4-weeks after baseline in relation to demographic, socio-economic, nicotine dependence, intervention, and health factors hypothesised to be associated with quitting outcomes. Results Hospital-referred patients comprised 26% of CSSS referrals, tended to be older, with lower socio-economic status and more long-term health conditions. Overall quitting success by people who made a CSSS supported quit attempt was 61% at 4-weeks, slightly lower than local averages, but similar to national averages. Our analysis sample contained records of 1,326 quit attempts that were supported by CSSS. Of the variables investigated, we found that receiving free NHS prescriptions was consistently associated with lower quitting success (Odds Ratio [OR] 0.55, 95% Confidence Interval [CI] 0.33-0.92), potentially because this is a proxy for lower socio-economic and health status. After accounting for other factors, having cancer relative to no health conditions was associated with higher quitting success (OR 2.26, 95%CI 1.18-4.33). Conclusion Ensuring patients continue seeking support to quit smoking after their interaction with hospital-based services can lead to quit rates comparable to other CSSS attendees who make a quit attempt. Our analyses highlight the importance of hospital and CSSS investment in improving the transfer of care between services.","PeriodicalId":506788,"journal":{"name":"medRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141265232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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